Indian National Association for the Study of the Liver Consensus Statement on Acute Liver Failure (Part 1): Epidemiology, Pathogenesis, Presentation and Prognosis

Abstract

Acute liver failure (ALF) is an infrequent, unpredictable, potentially fatal complication of acute liver injury (ALI) consequent to varied etiologies. Etiologies of ALF as reported in the literature have regional differences, which affects the clinical presentation and natural course. In this part of the consensus article designed to reflect the clinical practices in India, disease burden, epidemiology, clinical presentation, monitoring, and prognostication have been discussed. In India, viral hepatitis is the most frequent cause of ALF, with drug-induced hepatitis due to antituberculosis drugs being the second most frequent cause. The clinical presentation of ALF is characterized by jaundice, coagulopathy, and encephalopathy. It is important to differentiate ALF from other causes of liver failure, including acute on chronic liver failure, subacute liver failure, as well as certain tropical infections which can mimic this presentation. The disease often has a fulminant clinical course with high short-term mortality. Death is usually attributable to cerebral complications, infections, and resultant multiorgan failure. Timely liver transplantation (LT) can change the outcome, and hence, it is vital to provide intensive care to patients until LT can be arranged. It is equally important to assess prognosis to select patients who are suitable for LT. Several prognostic scores have been proposed, and their comparisons show that indigenously developed dynamic scores have an edge over scores described from the Western world. Management of ALF will be described in part 2 of this document.

Keywords: ACLF, acute on chronic liver failure; AFLP, acute fatty liver of pregnancy; AKI, Acute kidney injury; ALF, Acute liver failure; ALFED, Acute Liver Failure Early Dynamic; ALT, alanine transaminase; ANA, antinuclear antibody; AP, Alkaline phosphatase; APTT, activated partial thromboplastin time; ASM, alternative system of medicine; ASMA, antismooth muscle antibody; AST, aspartate transaminase; ATN, Acute tubular necrosis; ATP, adenosine triphosphate; ATT, anti-TB therapy; AUROC, Area under the receiver operating characteristics curve; BCS, Budd-Chiari syndrome; BMI, body mass index; CBF, cerebral blood flow; CBFV, cerebral blood flow volume; CE, cerebral edema; CHBV, chronic HBV; CLD, chronic liver disease; CNS, central nervous system; CPI, clinical prognostic indicator; CSF, cerebrospinal fluid; DAMPs, Damage-associated molecular patterns; DILI, drug-induced liver injury; EBV, Epstein-Barr virus; ETCO2, End tidal CO2; GRADE, Grading of Recommendations Assessment Development and Evaluation; HAV, hepatitis A virus; HBV, Hepatitis B virus; HELLP, hemolysis; HEV, hepatitis E virus; HLH, Hemophagocytic lymphohistiocytosis; HSV, herpes simplex virus; HV, hepatic vein; HVOTO, hepatic venous outflow tract obstruction; IAHG, International Autoimmune Hepatitis Group; ICH, intracerebral hypertension; ICP, intracerebral pressure; ICU, intensive care unit; IFN, interferon; IL, interleukin; IND-ALF, ALF of indeterminate etiology; INDILI, Indian Network for DILI; KCC, King's College Criteria; LC, liver cirrhosis; LDLT, living donor liver transplantation; LT, liver transplantation; MAP, mean arterial pressure; MHN, massive hepatic necrosis; MPT, mitochondrial permeability transition; MUAC, mid-upper arm circumference; NAPQI, n-acetyl-p-benzo-quinone-imine; NPV, negative predictive value; NWI, New Wilson's Index; ONSD, optic nerve sheath diameter; PAMPs, pathogen-associated molecular patterns; PCR, polymerase chain reaction; PELD, Pediatric End-Stage Liver Disease; PPV, positive predictive value; PT, prothrombin time; RAAS, renin–angiotensin–aldosterone system; SHF, subacute hepatic failure; SIRS, systemic inflammatory response syndrome; SNS, sympathetic nervous system; TB, tuberculosis; TCD, transcranial Doppler; TGF, tumor growth factor; TJLB, transjugular liver biopsy; TLR, toll-like receptor; TNF, tumor necrosis factor; TSFT, triceps skin fold thickness; US, ultrasound; USALF, US Acute Liver Failure; VZV, varicella-zoster virus; WD, Wilson disease; Wilson disease (WD); YP, yellow phosphorus; acute liver failure; autoimmune hepatitis (AIH); drug-induced liver injury; elevated liver enzymes, low platelets; sALI, severe acute liver injury; viral hepatitis.

Figure 1

Five phenotypes of liver failure. In (a), (b), and (c), there is no previously known liver disease. However, it is unclear if presence of a subclinical mild liver disease will change presentation, course, and outcome, e.g., in patients with nonalcoholic fatty liver, silent autoimmune hepatitis, Wilson disease, or inactive hepatitis B carrier state. Because classification is based on clinical presentation, phenotype concept helps to classify patients for planning management. ALF, acute liver failure; INR, international normalized ratio.

Figure 2

Role of gut microbiome in modulating liver injury. Bacterial products (PAMPs) as well as endotoxins initiate a proinflammatory response leading to cytokine storm and SIRS. It cannot be handled by the liver's immune apparatus which is grappling with a huge amount of DAMPs released by liver cell necrosis. PAMPs, pathogen-associated molecular patterns; DAMPs, damage-associated molecular patterns; LPS, lipopolysaccharaide; SIRS, systemic inflammatory response syndrome; TLR4, toll-like receptor 4; CARS, compensatory anti-inflammatory response syndrome.

Figure 3

Clinical course of acute liver failure as seen in Indian subcontinent after infection with a hepatitis virus. As liver dysfunction proceeds rapidly, patient may slide from stage of viral hepatitis to severe acute liver injury and then to (or often directly to) acute liver failure. Deterioration may be seen over a few hours, days or less often weeks. LT = liver transplantation.

Figure 4

MELD, Model For End-Stage Liver Disease.

Figure 5

Figure 6

Figure explaines the possible process of selecting a patient with ALF for transplantation. Red lines indicate patients hospitalized with low ALFED scores, and blue line, those with mid-level ALFED score. Green lines indicate patients hospitalized with high ALFED score 6. All patients should be counseled about possible need for transplantation, and patients listed if ALFED is more than 3. In an LDLT setting, donor workup should be started. The patient should be reassessed every 12 h to determine his/her response to conventional medical treatment. Transplant decision can be tailor made to the patient's evolving condition. ALFED score at day 3 is the best predictor of prognosis (See text). ALF, acute liver failure; ALFED, Acute Liver Failure Early Dynamic Model; LDLT, living donor liver transplantation; Tx, transplantation.